We propose to culture erythropoietic precursors from blood of patients with sickle cell anemia and other hemoglobinopathies using methylcellulose clonal cell culture technique and characterize their biosynthetic capabilities in culture with regard to the hemoglobins as well as other cellular proteins. We then relate the biochemical data to the current models of hemopoietic differentiation by combining biochemical and cell separation methods for erythropoietic precursors. After biochemical characterization is completed, we will develop experimental systems for studying the control mechanisms of hemoglobin synthesis under various conditions in order to define and hopefully manipulate the mechanisms of hemoglobin switching in culture. Concomitantly with these investigations, we propose to improve the primary cell culture technique for human erythropoietic precursors using combined biochemical and morphological approaches.